Abstract: The CD47 mimic protein of Borrelia burgdorferi is identified as p66 protein. Blocking the p66 protein on the pathogen Improves the immune response of an infected individual, and allows a more complete and/or more rapid resolution of Borrelia infection. The disclosure provides a method of inhibiting or treating an infection by a Borrelia pathogen, the method comprising administering an effective amount of an anti-p66 agent that reduces binding of p66 on the pathogen to signal regulatory protein a (SIRPa) on a phagocytic cell, where the agent (i) specifically binds to p66, or (ii) is a p66 polypeptide or derivative thereof.